The invention relates to implantable infusion devices for controllable in vivo delivery of drugs to a patient.
Implantable infusion devices provide a patient with an in vivo source of a drug to be administered, in a device which permits controlled delivery of the drug over a predetermined time period. Certain drugs, such as, for example, chemotherapy drugs and opioids, may be most effective if administered at a constant dose rate, instead of at discrete intervals.
A typical infusion device or pump includes a hermetically sealed outer housing which holds a vapor pressure fluid or other means for exerting a compressive force on a compressible or flexible inner drug reservoir which communicates with a drug delivery port. Alternatively, the drug may be disposed in the outer housing, with a propellant disposed in the inner housing. When the outer housing is filled with the drug, the propellant in the inner housing is compressed and changes state from a vapor to a liquid, thereby recharging the driving mechanism of the device. In still other embodiments, the outer housing may be divided into two chambers separated by a liquid-impermeable diaphragm. One chamber contains the drug and includes a drug delivery port, and the other chamber contains a propellant or spring member for exerting a force against the diaphragm so as to expel the drug through the delivery port.
The infusion device must meet numerous requirements for safety and efficacy. For example, the housing material must not react with body fluids or with the drugs and propellants inside the housing. Further, the membrane or flexible barrier between the chambers must not leak and must be impermeable to gas-phase fluids so as to prevent contamination of the drug with the propellant. Since the device is designed for implantation into a patient, great care must be taken to prevent any leakage of either the drug or the propellant into the patient""s body. In addition, the device is desirably as small and lightweight as possible so as to cause minimum invasive trauma, discomfort and disfigurement to the patient, yet sufficiently large to provide a useful therapeutic dosage of the drug being administered and minimize the frequency with which the device must be recharged. It is desirable to make the pump refillable so that it need not be surgically removed and replaced when the drug is depleted. However, refillability of the pump requires a port which is either outside of the skin or transcutaneously accessible without introducing infection or risking the release of an excessive and potentially harmful amount of the drug into the patient. Also, in those devices in which a propellant is contained within a flexible bag which expands and contracts in response to changes in the propellant pressure, it is necessary to ensure that introduction of the drug to the drug reservoir surrounding the propellant bag is not impeded by the presence and location of the bag in the reservoir and/or does not puncture or pinch the bag. Thus, it may be necessary to affix the propellant chamber or bag to the housing so as to avoid such problems. There is the additional problem of ensuring that the drug reservoir can be fully depleted and refilled, for optimum efficiency of the device.
Administration of a desired dosage of a drug over a period of time may require a controllable, constant flow of the drug from the device. However, as the drug is depleted from the reservoir, or if the force exerted on the drug reservoir cannot be controlled, a constant dose rate may be difficult to sustain.
U.S. Pat. No. 3,840,009 to Michaels et al. discloses a vapor pressure drug delivery device which has two chambers separated by a flexible wall or bladder. The outer chamber contains a drug to be administered to a patient, and the inner chamber contains a pressure fluid which expands to conform to the shape of the outer chamber, thereby enabling expulsion of substantially all of the drug within the outer chamber. The pressure fluid is maintained at a positive pressure at the temperature at which the device is used, so that no external power source is required.
U.S. Pat. No. 5,167,633 to Mann et al. discloses a medication infusion pump in which a constant pressure is exerted on a liquid medication to be administered. The pump includes a pressure reservoir in the form of a hollow enclosure with at least one flexible wall for containing a pressure fluid. The medication to be administered is outside of the pressure reservoir. The pressure fluid undergoes a phase change from a liquid to a vapor so as to expel the drug from the pump. The Mann et al. device is maintained at a negative pressure at the temperature of use to avoid leakage of medication from the pump into the patient.
U.S. Pat. No. 5,514,103 to Srisathapat et al. discloses a medication infusion pump including a drug reservoir and a pressure fluid reservoir which are separated by a movable wall or flexible bag. The pressure fluid reservoir includes a spacer therein to prevent contraction of the pressure fluid reservoir below a minimum volume which is slightly greater than the liquid phase volume of the pressure fluid, so that a portion of the pressure fluid always remains in a vapor phase. As a result, even when the drug reservoir is completely filled, the pressure fluid is not entirely in the liquid phase. Thus, additional energy to reinstate a vapor phase is not required.
U.S. Pat. No. 3,951,147 to Tucker et al. discloses a refillable implantable infusate pump in which a bellows containing a drug is contained within a housing which is filled with a pressure fluid or propellant. The Tucker et al. pump includes a filtering chamber to ensure removal of debris from the infusate drug prior to its delivery to the patient.
U.S. Pat. No. 5,045,064 to Idriss discloses a constant pressure implantable pump which employs shape-memory metal bands around a reservoir containing a fluid to be infused. The bands compress the reservoir containing the fluid to be infused, thereby eliminating the need for a propellant.
U.S. Pat. No. 5,395,324 to Hinrichs et al. discloses an infusion pump having a primary entry port leading to a drug reservoir, a separate bolus port leading to a bolus chamber, and means for ensuring that the bolus chamber is not inadvertently filled with the drug intended for the primary drug reservoir.
U.S. Pat. No. 5,769,823 to Otto discloses an implantable infusion pump which comprises a plastic housing, a bellows chamber enclosing a propellant, and two separate resilient plastic bags enclosing an infusate. The bags are surrounded by glycerin or the like which binds with any propellant passing through the bellows wall into the housing, thereby preventing passage of the propellant through the housing into the patient.
U.S. Pat. No. 5,575,770 to Melsky et al. discloses an implantable infusion pump having a valve-actuated bolus delivery chamber. Inadvertent administration of an overdose to the patient through the bolus delivery chamber is prevented by a design which requires the use of a side-access delivery needle, which is inserted through a pair of septa which are spaced apart to define a bolus chamber. The tip of the needle extends beyond the lower septum and depresses a lever to actuate the normally-closed valve. The side opening of the needle is disposed between the septa in the bolus chamber for delivery of the bolus dose to the bolus chamber. The design prevents erroneous dose delivery by requiring the simultaneous opening of the valve with delivery of the drug into the bolus using a side-access delivery needle.
It would be advantageous to provide an implantable infusion pump which is of simple construction and operation, made of lightweight materials, inexpensive to manufacture, efficient in the delivery of medicine, and easy to refill.
According to one aspect of the invention, there is provided an implantable infusion device, comprising a housing having an annular portion with an inner wall defining an interior region having a width dimension D and extending along a central axis, a bottom portion extending from the annular portion and spanning a first end of the interior region, and a top portion extending from the annular portion and spanning a second end of the interior region and being opposite the bottom portion, the interior region being substantially closed. The device further includes a closed fluid-impermeable hollow bellows extending from one of the top and bottom portions of the housing and defining a variable volume region therein and having a plurality of serially coupled annular members extending between top and bottom portions of the bellows. Junctions of the coupled annular members are coupled with flexures. The bellows has a maximum outer width dimension Dxe2x80x2 where Dxe2x80x2 is less than D. The portion of the housing from which the bellows extends includes a substantially planar annular peripheral portion disposed about a central portion. A pressure source is contained within the variable volume region of the bellows. The bellows is disposed within the interior region of the housing and rigidly coupled to the portion of the housing from which it extends. The annular members of the bellows are spaced apart from the annular portion of the housing. The housing includes a recharging fluid flow path from points external to the housing to a region adjacent to the central portion of the portion of the housing from which the bellows extends. The housing further defines a fluid exit flow path extending from the region between the bellows and the annular portion of the housing to points external to the housing.
The device further includes a pierceable, self-sealing septum disposed in the recharging fluid flow path and may further include a recharging fluid reservoir disposed along the recharging fluid flow path. The septum may be removable from the housing.
The device further includes at least one of a flow restrictor and a filter disposed along the fluid exit flow path.
In one embodiment, the housing is made of a gas-impermeable material, and the bellows which encloses the pressure source is made of a substantially rigid, gas-impermeable material. In a preferred embodiment, the bellows is hermetically sealed.
The pressure source comprises one or more of the group consisting of multiple-phase fluids, springs, shape memory metal alloys, Belville washers, and compressible materials. In one embodiment, a multiple-phase fluid propellant is present in at least one of a liquid phase and a gas phase within the variable volume region of the bellows as a function of ambient temperature. Conversion of the propellant fluid from a liquid phase to a gas phase increases the volume displaced by the bellows in the interior region of the housing, thereby exerting a force on a fluid external to the bellows in the housing so as to provide a substantially constant flow rate of the fluid through the fluid exit flow path.
In a preferred embodiment, the propellant is disposed in the variable volume region of the bellows at a pressure which is not less than atmospheric pressure at ambient temperature.
In one embodiment, the central portion of the bellows is offset from the plane of the annular peripheral portion of said bellows. A central region of the portion of the housing from which the bellows extends is correspondingly offset from the plane of the annular portion of the housing. The offset central region of the housing substantially nests within the offset central portion of the bellows.
In one embodiment, the housing and bellows are cylindrical.
The device can further include a separate bolus port in fluid communication with the fluid exit flow path. The bolus port can include a pair of septa which are spaced apart to define a bolus reservoir therebetween. A side-access delivery needle having an opening near the center of its length is required to delivery a bolus dose of the infusate to the bolus reservoir.
In one preferred embodiment, the bellows extends from the top portion of the housing. In another preferred embodiment, the bellows extends from the bottom portion of the housing.
According to another aspect of the invention, there is provided an implantable infusion device, comprising a housing having an annular portion with an inner wall defining an interior region having a width dimension D and extending along a central axis, a bottom portion extending from the annular portion and spanning a first end of the interior region, and a top portion extending from the annular portion and spanning a second end of the interior region, the top portion being opposite the bottom portion, the interior region being substantially closed. The device further includes a closed fluid-impermeable hollow bellows disposed about a variable volume region and having a top member, a bottom member, and a plurality of serially coupled annular members extending therebetween. Junctions of the coupled annular members are coupled with flexures. The bellows has a maximum outer width dimension Dxe2x80x2 where Dxe2x80x2 is less than D. At least one of the top and bottom members includes a substantially planar annular peripheral portion disposed about a central portion. A pressure source is contained within the variable volume region of the bellows, and the bellows is disposed within the interior region of the housing with one of the top and bottom members facing and rigidly coupled to a corresponding portion of the housing. The annular members of the bellows are spaced apart from the annular portion of the housing. The housing includes a recharging fluid flow path from points external to the housing to a region adjacent to the central portion of one of the top and bottom members of the bellows. The region of coupling between the housing and the bellows defines a fluid dispersal flow path from the region adjacent to the central portion of the coupled member of the bellows to a region between the annular members of the bellows and the annular portion of the housing. The housing further defines a fluid exit flow path extending from the region between the bellows and the annular portion of the housing to points external to the housing.
In one embodiment, a central portion of at least one of the top and bottom members of the bellows is offset from the plane of the annular peripheral portion of the top and bottom members of the bellows. A central region of the portion of the housing which is coupled to the bellows is correspondingly offset from the plane of the annular portion of the housing, so that the offset central region of the portion of the housing which is coupled to the bellows substantially nests within the central portion of the coupled portion of the bellows.
In one preferred embodiment, the bellows is coupled to the top portion of the housing. In another preferred embodiment, the bellows is coupled to the bottom portion of the housing.
According to still another aspect of the invention, there is provided a septum replacement kit for an enclosed device which is sealed with a septum, wherein the enclosed device defines a fluid reservoir, a fluid flow inlet and a fluid flow outlet. The kit comprises a compressible septum adapted to sealingly engage in the fluid flow inlet of the reservoir, and a septum installation tool adapted to compress the septum to a nominal insertion size, maintain the nominal insertion size of the septum prior to installation of the septum, and install the septum in the fluid flow inlet of the reservoir.
The septum installation tool preferably comprises a tubular member adapted for insertion into the fluid flow inlet of the reservoir, an opening in the tubular member for insertion and retention of the septum therein, and a plunger member disposable in the tubular member for expulsion of the septum from the tubular member. Insertion of the septum into the tubular member compresses the septum. Expulsion of the septum from the tubular member into the fluid inlet reservoir permits the septum to expand to fill in and seal the fluid inlet reservoir.
The septum is preferably made of a pierceable, self-sealing elastomeric or rubber-like material.
These and other objects and advantages of the invention will in part be obvious and will in part appear hereinafter. The invention accordingly comprises the apparatus possessing the construction, combination of elements and arrangement of parts which are exemplified in the following detailed disclosure, the scope of which will be indicated in the claims.